This proposal is for a five year renewal of the Alzheimer Disease Cooperative Study (ADCS). This consortium of 31 academic medical centers is proposing to continue to carry out clinical drug trials for promising new agents designed to ameliorate behavioral symptoms, improve cognition, slow the rate of decline or delay the appearance of Alzheimer's disease (AD). In addition, the consortium will continue to evaluate instruments designed to measure outcomes in clinical drug trials of AD subjects. In our new grant application, the ADCS will test previously developed ADCS instruments in actual clinical drug trials. We will also expand the range of patients studied by the ADCS to include patients with mild cognitive decline who are "at risk" for AD and we will study agitated subjects in nursing homes. A major effort is planned to expand the recruitment of minority groups into AD clinical trials. New methods for evaluating quality of life and the pharmacoeconomic impact of AD treatment will be developed. Trials proposed in this current application are directed towards both cognitive and behavioral symptoms. The trials designed to improve cognition or slow the rate of decline include: 1) a trial of antioxidants for patients who are "at risk" for the development of dementia, 2) a trial of anti-inflammatory agents (hydroxychloroquine and colchicine) to slow progression in AD, and 3) a trial of an agent that may upregulate endogenous neurotrophins (MT082). Three behavioral symptoms will be targeted for treatment including 1) sleep disturbance (melatonin), 2) agitation in the nursing home (valproate), and 3) depression (paroxetine).